PHASE II RANDOMIZED STUDY OF VACCINE TREATMENT OF ADVANCED PROSTATE CANCER (E7897): A TRIAL OF THE EASTERN COOPERATIVE ONCOLOGY GROUP. A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated. A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses. The prime/ boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1% demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells. Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease.ANTIANDROGEN, VACCINE AND COMBINATION THERAPY IN PATIENTS WITH NONMETASTATIC HORMONE REFRACTORY PROSTATE CANCER. There is no current standard treatment for patients with prostate cancer who have received hormonal therapy but have an increasing prostate specific antigen (PSA) without radiographic evidence of metastasis. This trial was designed to analyze toxicity, immunogenicity and time to treatment failure using vaccine, antiandrogen therapy or their sequential use. A total of 42 patients were randomized to receive vaccine versus antiandrogen therapy with nilutamide. The vaccine consisted of recombinant vaccinia viruses containing the PSA and B7.1 costimulatory genes as prime vaccinations, and avipox-PSA as boosters. After 6 months patients with an increasing PSA and no metastasis may receive a combination of both treatments. Three patients on nilutamide were removed from study secondary to grade 3 toxicities but no grade 3 toxicities were attributed to vaccine. In the vaccine arm median time to treatment failure was 9.9 months with 13 of 21 decreases in PSA velocity versus 7.6 months with 16 of 21 decreases in PSA velocity in the nilutamide arm (p =0.28). Of the patients in the nilutamide arm 8 had vaccine added at the time of PSA progression. Median time to treatment failure with combined therapy was 5.2 months, with a median duration from study entry of 15.9 months. Of the patients in the vaccine arm 12 had nilutamide added at the time of PSA progression. Median time to treatment failure with combined therapy was 13.9 months and a median of 25.9 months from initiation of therapy. Further studies are merited to investigate the role of combining vaccine with antiandrogen therapy or vaccine followed by vaccine plus antiandrogen therapy in this patient population.